Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33.
In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or FcepsilonRI-activation, and enhances FcepsilonRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-kappaB and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.
Pecaric-Petkovic
Tatjana
T
Institute of Immunology, University Hospital Bern, Inselspital, Bern, Switzerland.
Didichenko
Svetlana A
SA
Kaempfer
Sacha
S
Spiegl
Nicole
N
Dahinden
Clemens A
CA
D001491:Basophils / Q000166:cytology / Q000276:immunology*; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D015936:Complement C5a / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D017997:Leukotriene C4 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D018106:CD28 Antigens; D017252:CD3 Complex; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; C508598:IL4 protein, human; D007375:Interleukin-1; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D020382:Interleukin-18; D007377:Interleukin-3; D000067596:Interleukin-33; D016209:Interleukin-8; D007378:Interleukins; D011956:Receptors, Cell Surface; D015847:Interleukin-4; D017997:Leukotriene C4; D015936:Complement C5a